Increased gene expression of catecholamine-synthesizing enzymes in adrenal glands contributes to high circulating catecholamines in pigs with tachycardia-induced cardiomyopathy

High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (hf). however,it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal hf models. we analyzed the mrna levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (th),aromatic l-amino acid decarboxylase (aaad),dopamine-β-hydroxylase (dbh) and phenylethanolamine n-methyltransferase (pnmt) in adrenal glands of 18 pigs with chronic systolic non-ischaemic hf (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 shamoperated controls. pigs with severe hf demonstrated an increased expression of th and dbh (but neither aaad nor pnmt) as compared to animals with milder hf and controls (p<0.05 in all cases). the increased adrenal mrna expression of th and dbh was accompanied by a reduced left ventricle ejection fraction (lvef) (p<0.001) and an elevated plasma b-type natriuretic peptide (bnp) (p<0.01),the other indices reflecting hf severity. there was a positive relationship between the increased adrenal mrna expression of th and dbh,and the high levels of circulating adrenaline and noradrenaline (all p<0.05). the association with noradrenaline remained significant also when adjusted for lvef and plasma bnp,suggesting a significant contribution of adrenals to the circulating pool of catecholamines in subjects with systolic hf. © 2015,polish physiological society. all rights reserved.